Al-Risi Elham S, Al-Essry Fatma S, Mula-Abed Waad-Allah S
Oman Medical Specialty Board, Muscat, Oman.
Department of Chemical Pathology, Directorate of Laboratory Medicine and Pathology, Royal Hospital, Muscat, Oman.
Oman Med J. 2017 Sep;32(5):365-370. doi: 10.5001/omj.2017.71.
To evaluate the significance of serum chromogranin A (CgA) status in patients with and without different neuroendocrine tumors (NETs) by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman.
We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014). During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11-86 years and mean±standard deviation (SD) 44.0±18.0 years), were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L.
Of the 302 CgA tests reviewed, 197 (65.2%) were within the quoted normal range; however, 105 (34.8%) had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5%) had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3%) patients with CgA > 22 IU/L (83.0±116.0 IU/L) who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus). Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L). The overall clinical sensitivity of CgA in the diagnosis of NETs was 84.2%, overall specificity was 78.2%, positive predictive value was 41.5%, negative predictive value was 96.4%, and overall efficiency was 79.2%. In patients with individual NET, a good reflection in CgA was noticed in the follow-up period following surgery or therapy.
Serum CgA is a sensitive and effective noninvasive laboratory test for the clinical detection and management of NETs. Awareness of the pitfalls of the tests in patients with non-NET conditions, particularly chronic diseases and use of certain drugs, is important to be considered during the interpretation of the CgA levels.
通过对阿曼一家三级护理医院中嗜铬粒蛋白A（CgA）作为神经内分泌肿瘤（NETs）生物标志物的诊断效用和局限性进行回顾性评估，来评价血清CgA状态在有无不同NETs患者中的意义。
我们对阿曼皇家医院临床生物化学实验室在24个月期间（2012年4月至2014年3月）接到的CgA检测申请进行了回顾性分析。在此期间，共收到针对270例患者（119例男性和151例女性；年龄范围11 - 86岁，平均±标准差（SD）为44.0±18.0岁）的302次CgA检测申请。在这些CgA检测中，245次检测是针对245例接受NETs诊断调查的患者进行的，57次CgA检测是针对25例已确诊NETs且正在接受随访的患者进行的。血清CgA水平采用酶联免疫吸附测定法进行分析，临界值设定为22 IU/L。
在审查的302次CgA检测中，197次（65.2%）在公布的正常范围内；然而，105次（34.8%）的CgA>22 IU/L。在245例进行一线CgA检测的患者中，38例（15.5%）患有NETs，包括类癌、嗜铬细胞瘤、胰腺NET、肾上腺腺瘤、前列腺腺癌、胃肠道NET、甲状腺髓样癌、神经鞘瘤、肺小细胞癌、甲状旁腺腺瘤和垂体大腺瘤。这些NETs患者中CgA的平均±SD为205.0±172.0 IU/L。同时，有45例（18.3%）CgA>22 IU/L（83.0±116.0 IU/L）的患者未患有NETs。这些病症包括：原发性高血压、慢性肾脏病、心力衰竭、消化性溃疡、慢性腹泻、使用质子泵抑制剂以及其他慢性疾病（甲状腺功能减退、哮喘、糖尿病）。在25例已知患有NETs且接受随访的患者中，有57次CgA检测结果（29次CgA≤22 IU/L，28次CgA>22 IU/L）。CgA在NETs诊断中的总体临床敏感性为84.2%，总体特异性为78.2%，阳性预测值为41.5%，阴性预测值为96.4%，总体效率为79.2%。在患有个体NET的患者中，术后或治疗后的随访期间CgA能很好地反映病情。
血清CgA是用于NETs临床检测和管理的一种敏感且有效的非侵入性实验室检测。在解释CgA水平时，认识到非NET病症患者（特别是慢性疾病患者和使用某些药物的患者）检测中的陷阱很重要。
